The objectives of this reserch is to elucidate the molecular basis of the catabosism of VLDL-related lipoproteins by the liver. In particular, we wish to determine the role that carbohydrate moiety of VLDL-apoproteins plays in the hepatic removal of VLDL remnants. Well-defined structrual alterations in rat VLDL will be introduced by specific chemical and enzymatic modifications. The resulting VLDL derivatives will be compared with regard to their binding, uptake, and degradation by the liver. We shall study this problem by means of the following approaches: (a) The structural features of VLDL remnants required for recognition by hepatic membrane receptors will be deduced by studying the specific binding of VLDL derivatives and VLDL remnants to rat hepatic plasma membranes. (b) The intracellular "VLDL pathway" (uptake and degradation) will then be explored. Rat liver cells in culture will be used in these studies. We shall determine whether the VLDL derivatives with maximal affinity for the hepatic membrane are also the most effective ones in regulating lipid biosynthesis in liver cells. (c) Finally, the intact rat will be employed to study the partition of VLDL between conversion to LDL and degradation by the liver. These experiments are intended to evaluate in vivo the results obtained in vitro. In sum, the experiments are meant to determine whether there are specific structural features which determine the catabolism of VLDL and to identify those features.